Details

Autor(en) / Beteiligte

• Perlman, Signe
• van den Hazel, Bart
• Christiansen, Jesper
• Gram-Nielsen, Sanne
• Jeppesen, Claus B
• Andersen, Kim V
• Halkier, Torben
• Okkels, Sigurd
• Schambye, Hans T

Titel

Glycosylation of an N-Terminal Extension Prolongs the Half-Life and Increases the in Vivo Activity of Follicle Stimulating Hormone

Ist Teil von

• The journal of clinical endocrinology and metabolism, 2003-07, Vol.88 (7), p.3227-3235

Ort / Verlag

Bethesda, MD: Endocrine Society

Erscheinungsjahr

2003

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• FSH is a key component in assisted reproductive technologies. Because of rapid clearance of the hormone, patients have to be treated with daily injections. To address this problem, a long-acting FSH mutein was created by introduction of additional N-linked glycosylation into the molecule. New glycosylation sites were introduced by two different approaches: structure-aided, site-directed introduction of sites within the FSH molecule and addition of N-terminal extensions. A mutein with the extension sequence ANITVNITV at the N terminus of the α-chain (FSH1208) was efficiently glycosylated at both new sites. This resulted in a molecule with increased size and charge, factors known to reduce renal clearance of proteins. FSH1208 was found to have a 3- to 4-fold increased serum half-life, compared with wild-type recombinant FSH. Furthermore, in spite of a lower in vitro activity, FSH1208 had a markedly increased in vivo potency, as shown by increased ability to augment the ovarian weight and stimulate the serum estradiol levels in rats. These characteristics make FSH1208 a possible candidate for improved infertility treatment.